What are plexiform neurofibromas?
Plexiform neurofibromas (PNs) are benign tumours that grow along nerves. They commonly occur in children with neurofibromatosis type 1 (NF1), with approximately 30-50% of children with NF1 having PNs. These tumours occur due to variations in the NF1 gene, which leads to abnormal growth of the tissue that covers and protects the nerves (nerve sheath cells).
PNs are a type of neurofibroma that grow along multiple nerve branches in the body. They are often described as having a soft, irregular texture and can vary in size and location. The tumours can occur anywhere from the skin’s surface to deep within the body’s tissues, including vital organs.
While PNs may sometimes cause pain or changes to your child’s appearance, many children can lead active, fulfilling lives with early diagnosis, regular monitoring and access to targeted therapies.
What are symptoms of plexiform neurofibromas?
The symptoms of PNs depend on the location of the tumour in the body. Regardless of the part of body in which the PN is located, some general symptoms that indicate tumour growth include:
- lumps on or under the skin that feel like hard knots
- café-au-lait spots—flat, darkened, oval-shaped marks on the skin overlying the lesion
- pain, tenderness, or swelling
- disfigurement, numbness, tingling or weakness/stiffness in the affected area caused by compression of the nerves.
These symptoms may occur on their own or together, depending on the size and location of the PN.
Head, face and neck
For PNs located in the head, face and neck, symptoms may include:
- visible swelling
- vision changes (if involving the eye socket)
- numbness and weakness of the face
- difficulty swallowing or breathing
- possible headaches or pressure symptoms.
Arms and legs
For PNs located in the limbs (arms and legs), symptoms may include:
- weakness in the limbs
- reduced range of mobility
- visible lumps/masses
- difficulties with coordination.
Spine
For PNs located in the spine, symptoms may include:
- back pain
- numbness or tingling in the affected area
- weakness in the limbs
- paralysis (if the spinal cord or nerve roots are compressed)
- changes in bladder or bowel function (more severe cases).
Internal organs
PNs that occur in the torso/internal organs, can lead to:
- difficulty breathing, if near the lungs and airways
- abdominal pain
- changes in bowel function
- urinary symptoms, due to direct compression of the kidneys, bladder or ureters.
What causes plexiform neurofibromas?
PNs are usually caused by genetic variation associated with NF1. The tumours develop because of a genetic variant in the NF1 gene, which normally functions to produce neurofibromin – a protein that helps to regulate cell growth, preventing tumour formation.
When a child has a genetic variant of the NF1 gene, neurofibromin either is absent or dysfunctional in the body, allowing abnormal cells to reproduce uncontrollably. This leads to the formation of tumours such as PNs.
A variation of the NF1 gene can be inherited from a parent or it may occur spontaneously or at random during fetal development. There is no evidence of environmental factors like diet, lifestyle or exposure that increases one’s likelihood of developing PNs.
What are the risk factors for developing plexiform neurofibromas
Having NF1 is the main risk factor of developing PNs. About 30-50% of people with NF1 will develop at least one PN during their lifetime. During times of hormonal changes like puberty or pregnancy, tumours may grow more rapidly due to hormonal fluctuations.
How many other children have plexiform neurofibromas?
PNs occur almost exclusively in children with NF1. NF1 affects roughly 1 in 3,000 children worldwide. While PNs are very rare tumours in the general pediatric population, they are relatively common complications among children with NF1, with as many as one in four children with NF1 experiencing PNs.
How are plexiform neurofibromas diagnosed?
PNs are usually diagnosed through a combination of clinical evaluation, genetic testing and imaging. As it is associated with NF1, diagnosis may begin with a clinical evaluation looking for signs of NF1 such as cafe-au-lait spots, skin neurofibromas and assessment of family history. To confirm the diagnosis, genetic testing may also be done, especially in young children or those with subtle symptoms.
For PN diagnosis and assessment, magnetic resonance imaging (MRI) is used to provide detailed, radiation-free images of tumours to determine their size, location and impact on nerves and surrounding tissues.
Biopsy is not typically needed for diagnosis.
How are plexiform neurofibromas treated?
Surgery
PNs can be surgically removed or reduced in size, especially when the tumours cause significant symptoms or complications. However, PNs are often involved in multiple nerve branches, making them difficult or impossible to remove completely. The risks of surgically removing PNs include recurrence (the tumours growing back), nerve injury, weakness/stiffness and bleeding.
Medication
Newer treatments for PNs include targeted medications called mitogen-activated extracellular kinase (MEK) inhibitors. These work by blocking MEK1/2 proteins, which control cell growth. By blocking these proteins, MEK inhibitors stop growth signals in cancer cells, particularly in tumors like NF1-associated PNs.
There are two MEK inhibitors currently available to treat inoperable, symptomatic PNs in children, selumetinib and mirdametinib. If your child’s PNs are being treated with a MEK inhibitor, they will be given medication by mouth and closely monitored by MRI and assessment of their symptoms. Common side effects of these medications include rash, gastrointestinal (GI) symptoms (i.e., nausea, vomiting and diarrhea), and fatigue. More rare but serious effects include muscle damage, heart failure, and functional or structural damage to the eye.
The optimal treatment recommended by your child’s health-care team will depend on the severity of your child’s symptoms.
Complications
PNs can cause complications—depending on their size and location—such as pain, weakness/stiffness or changes in your child’s appearance. Their growth pattern can sometimes make surgical removal challenging, and tumours often require careful, ongoing monitoring.
While most PNs remain benign, a small percentage (8-12%) may become cancerous peripheral sheath tumours in adulthood. It is important to regularly monitor PNs to detect these types of changes early.
How to help your child at home
Support your child by minimizing the risks of complications and the impact on their quality of quality of life:
- Protect the tumour site(s) from injury or repeated pressure, as fragile blood vessels within the tumours are prone to bleeding and swelling. Encourage safe and gentle activities to minimize injuries.
- Report any new changes immediately to your child’s health-care team.
- Attend scheduled medical appointments so your child’s health-care team can regularly monitor your child’s PNs.
- Maintain good skin hygiene around the tumour site(s) to avoid infections, which could worsen symptoms.
What is the outcome for a child with plexiform neurofibroma?
NF1-associated PNs can be managed with targeted therapy and monitoring. Approximately seven out of 10 children experience significant tumour shrinkage with the use of MEK inhibitors. Children on MEK inhibitors also commonly experience a reduction in pain and improvement in daily function and quality of life. While children with PNs can benefit from the use of these targeted therapies, it is still uncertain how long they need to be maintained on therapy to benefit long term.
Recurrence of plexiform neurofibroma
PNs may sometimes grow back or progress after treatment. For tumours treated with surgery, whether the tumour comes back (recurrence) can depend on how much of the tumour was first removed.
When to see a health-care provider
Schedule a visit with your child’s health-care team if:
- you notice new or worsening localized symptoms including increased pain, swelling, or changes in the size of the tumour(s).
- you notice symptoms affecting the whole body, including, fever, fatigue, skin rashes, or unexplained weight loss.
- neurological symptoms develop (i.e., numbness, weakness, difficulty moving).
- your child experiences side effects from treatment (e.g., from MEK inhibitors).
When to visit the Emergency Department
Got the Emergency Department right away if the tumour suddenly grows rapidly, causes severe or uncontrollable pain, or leads to sudden severe nerve problems. Difficulty breathing or swallowing, signs of infection or any bleeding related to the tumour also require prompt medical attention.
When to call 911
Call emergency services immediately if your child has sudden severe neurological issues (i.e., paralysis, loss of consciousness), severe breathing difficulties or choking, heavy uncontrolled bleeding, or signs of shock. These represent life-threatening emergencies that require immediate intervention.
References
Gross, Andrea M., et al. “Selumetinib in children with inoperable plexiform neurofibromas.” New England Journal of Medicine 382. 15 (2020): 1430-1442.
Prada, Carlo E., et al. “Pediatric plexiform neurofibromas: impact on morbidity and mortality in neurofibrmatosis type 1.” The Journal of Pediatrics 160.3 (2012): 461-467.
Lafay-Cousin L, et al. “A National Modified Delphi Consensus on the Referral and Management of NF1 Plexiform Neurofibroma.” Canadian Journal of Neurological Sciences 2025 Sep 2:1-9. Epub ahead of print.